The current proposal is in response to the recent RFA announcement (RFA-MH-09-172) and is aimed at "validating the use of particular biomarkers associated with autism." We propose to evaluate dynamic pupillary light reflex (PLR) as a potential biomarker for autism. PLR refers to the involuntary response whereby the pupil size changes in response to a short flash light. Our recent preliminary study revealed that individuals with autism showed significantly longer constriction latencies and smaller constriction amplitudes as compared to unaffected individuals. PLR may represent a promising biomarker in that PLR latencies served as an effective discriminator (89.6%) between affected and unaffected individuals within our pilot sample (22 children with autism and 44 controls). The goal of the present proposal is to further validate and explore the aforementioned preliminary findings by testing a large group of diversified and more heterogeneous participants (a total of 100 children with ASDs and equal number of controls). The two specific aims are: (1) to validate our preliminary results and investigate whether the combined atypical PLR parameters are associated with only a subgroup of children with autism and whether they are associated with non-specific brain dysfunctions;and (2) To test whether our observed atypical PLR parameters are associated with non-specific impairments in autonomic nervous system (ANS). These studies will allow for further evaluation of the specificity and generalizability of PLR as a potential biomarker for ASD. The PLR testing procedure is low-cost, non-invasive, objective, and has the potential to be implemented for very young children. This proposed R21 project will generate results that can help us validate and better understand our preliminary observations. It is anticipated that as functional biomarkers, the pupillary light reflex measurements will advance our understanding of neurodevelopmental differences in the autism brain. PUBLIC HEALTH RELEVANCE: Pupillary light reflex (PLR) is a simple objective measure of neurological functions. Our preliminary study has revealed that individuals with autism showed significantly longer constriction latencies and smaller constriction amplitudes. The proposed study will validate our preliminary results in a large heterogeneous group of participants. And we will clarify whether the atypical PLR parameters are associated with mental retardation and autonomic nervous system dysfunction in general.